PB1822: A CASE OF EXTRAMEDULLARY ACUTE MYELOID LEUKEMIA SUCCESSFULLY TREATED WITH NOVEL AGENTS
Authors: V. Gianfelici, L. Levato, D. Magro, E. Piro, C. Santamaria, L. Scalise, P. Marinaro, D. Loiacono, A. Mannella, A. Russo, L. Tucci, M. Rossi
Journal: HemaSphere (2022)

Background: Extramedullary acute myeloid leukemia (eAML) is a relatively rare clinical presentation, that carries a poor prognosis and poses therapeutic dilemmas. Treatment intensification with allogeneic hematopoietic cell transplantation (alloHCT) is often recommended for concurrent extramedullary and bone marrow (BM) involvement. In the last years, novel drugs have been approved for AML treatment, though their efficacy in eAML needs to be clarified. We here describe a case of therapy-related AML (tAML) with NPM1 mutation and cutaneous localization that achieved complete remission (CR) with CPX-351. Unfortunately, she developed a meningeal relapse followed by medullary relapse with acquired FMS-like tyrosine kinase 3 (FLT3) internal tandem duplications (ITD) mutation. Aims: To define the genetic profile and the efficacy of novel drugs in eAML. Methods: The diagnosis of AML was established according to the WHO. Flow cytometry analysis was performed by FACSCanto Instrument on BM and cerebrospinal fluid (CSF). Cytogenetic analyses (G-banding) were performed on BM at diagnosis and relapse. Molecular analysis at diagnosis and relapse included NPM1, FLT3-ITD and -TKD. NPM1 monitoring was performed after induction and consolidation. Cutaneous involvement was documented by biopsy. Results: A 56 year-old woman, previously treated for choriocarcinoma, presented to our Institution because of leukocytosis, anemia and diffuse cutaneous lesions. BM examination was consistent with a diagnosis of AML with monocytic differentiation, while cutaneous biopsy showed a dermic infiltration of leukemic cells. Chromosome analysis showed a normal karyotype, but molecular analysis revealed the NPM1 mutation with wild-type conformation of FLT3 gene. Even with a favorable molecular profile, she was considered a high-risk patient as of tAML and leukemia cutis, thus eligible for alloHCT. She underwent induction and 2 cycles of consolidation with CPX-351. After induction, she obtained a complete hematological and molecular response with complete disappearance of cutaneous nodules. Three months after CR, she complained headache, diplopia and paralysis of the right eyes. CSF examination showed a meningeal relapse of AML while BM biopsy confirmed the haematologic and molecular remission. She was treated with intrathecal methotrexate and cytarabine (ITC) given bi-weekly until achievement of morphological and cyto-fluorimetric CSF-remission. After the XII ITC, the patient developed anemia and leukopenia. BM and CSF examination revealed concomitant BM and CSF relapse. Rescue therapy with high dose cytarabine was promptly started. Subsequently, molecular analysis documented NPM1 mutations in 4% of cells and the acquisition of FLT3-ITD in 40% of cells. Based on these data, second generation FLT3 inhibitor gilteritinib was chosen due to previous reports of crossing hemato-encephalic barrier. The drug was started from day 8 at 120 mg/day. Treatment was well-tolerated. She obtained second CR and at time of writing she was waiting for a familiar alloHCT. Targeted next-generation sequencing by Illumina MiSeq is ongoing. Summary/Conclusion: This is the first report of a positive effect of CPX-351 in cutaneous localization of AML, while few cases have been reported about the effect of gilteritinib in meningeal sarcoma. Furthermore, the case here reported underlines the importance of FLT3 retesting at relapse. Overall, these data suggest to design ad hoc studies in eAML to clarify the genetic profile and the effect of novel drugs in this setting.